Vimizim

Mucopolysaccharidosis (MPS) Agents

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
The solution should be clear to slightly opalescent and colorless to pale yellow when diluted. A diluted solution with slight flocculation (e.g., thin translucent fibers) is acceptable for administration.

Prepare and administer this product under the supervision of a healthcare professional with the ability to manage medical emergencies.
 
Dilution
Dilute the calculated dose in 0.9% NaCl to a final volume of 100 mL or 250 mL depending on the patient's weight:
For patients weighing < 25 kg, the final volume should be 100 mL.
For patients weighing >= 25 kg, the final volume should be 250 mL.
Avoid agitation during preparation. Gently rotate the bag to ensure proper distribution. Do not shake the solution.
Vials are for single-use only. Discard any unused product.
Storage: Use immediately after dilution; vial does not contain preservatives. If immediate use is not possible, diluted product may be stored for up to 24 hours at 2—8 degrees C (36—46 degrees F) followed by up to 24 hours at 23—27 degrees C (73—81 degrees F). Administration should be completed within 48 hours from the time of dilution. Protect from light.
 
Intermittent IV Infusion
Administer the diluted solution using a low-protein binding infusion set equipped with a low-protein binding 0.2 micrometer in-line filter.
The rate of infusion depends on patient weight and tolerance:
For patients weighing < 25 kg: Begin the infusion at a rate of 3 mL/hr for the first 15 minutes, and then, if tolerated, the infusion rate may be increased to 6 mL/hr for the next 15 minutes. If this rate is tolerated, then the rate may be increased every 15 minutes in 6 mL/hr increments (Max: 36 mL/hr). The total volume of the infusion should be delivered over a minimum of 3.5 hours.
For patients weighing >= 25 kg: Begin the infusion at a rate of 6 mL/hr for the first 15 minutes, and then, if tolerated, the infusion rate may be increased to 12 mL/hr for the next 15 minutes. If this rate is tolerated, then the rate may be increased every 15 minutes in 12 mL/hr increments (Max: 72 mL/hr). The total volume of the infusion should be delivered over a minimum of 4.5 hours.
Slow, temporarily stop, or discontinue the infusion rate if a hypersensitivity reaction occurs.
Do not infuse with other products in the infusion tubing. Compatibility with other products has not been evaluated.

serious hypersensitivity reactions or anaphylaxis / Rapid / 7.7-7.7
cyanosis / Early / Incidence not known
spinal cord compression / Delayed / Incidence not known

antibody formation / Delayed / 100.0-100.0
dyspnea / Early / Incidence not known
erythema / Early / Incidence not known
hypotension / Rapid / Incidence not known
peripheral edema / Delayed / Incidence not known

fever / Early / 33.0-33.0
vomiting / Early / 31.0-31.0
headache / Early / 26.0-26.0
nausea / Early / 24.0-24.0
abdominal pain / Early / 21.0-21.0
chills / Rapid / 10.3-10.3
fatigue / Early / 10.3-10.3
flushing / Rapid / Incidence not known
urticaria / Rapid / Incidence not known
cough / Delayed / Incidence not known
rash / Early / Incidence not known

Vimizim

Rx

Enzyme replacement therapy
Used for Morquio A (an autosomal recessive lysosomal storage disorder)
Risk of anaphylaxis; carefully monitor during/after administration

2 mg/kg/dose IV administered once weekly. Premedication with antihistamines with or without antipyretics 30 to 60 minutes prior to the infusion is recommended.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

There are no drug interactions associated with Elosulfase alfa products.

Vimizim Intravenous Inj Sol: 1mg, 1mL

2 mg/kg/week IV.

2 mg/kg/week IV.

2 mg/kg/week IV.

>= 5 years: 2 mg/kg/week IV.
< 5 years: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) is an autosomal recessive lysosomal storage disorder that is caused by a mutation in the gene encoding N-acetylgalactosamine-6-sulfatase (GALNS). Patients with MPS IVA have an absence or marked reduction of GALNS activity, which leads to the accumulation of the glycosaminoglycan (GAG) substrates keratan sulfate (KS) and chondroitin-6-sulfate (C6S). Patients experience widespread tissue and organ damage, but the course of progression and severity is variable. Elosulfase alfa is intended to provide exogenous N-acetylgalactosamine-6-sulfatase. Elosulfase alfa uptake by cells into lysosomes is mediated by the binding of mannose-6-phosphate-terminated oligosaccharide chains of elosulfase alfa to mannose-6-phosphate receptors. Once inside the lysosomes, the catabolism of GAGs KS and C6S is thought to be increased.
 
NOTE: Because an animal model that recapitulates the human disease phenotype was not available, the activity of elosulfase alfa was evaluated using human primary chondrocytes from two MPS IVA patients. In this model, treatment with elosulfase alfa induced clearance of KS lysosomal storage from the chondrocytes.

Elosulfase alfa is administered via intravenous infusion.
 
Affected cytochrome P450 enzymes: none

Elosulfase alfa pharmacokinetics were evaluated in 23 patients (ages 5—41 years) with Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) who received 2 mg/kg/dose IV weekly for 22 weeks. Doses were infused over approximately 4 hours. The following mean PK parameters were reported:
 
Week 0                                                  Week 22
     Cmax = 1.49 +/- 0.534 mcg/mL                   Cmax = 4.04 +/- 3.24 mcg/mL
     Tmax = 172 +/- 75.3 min                           Tmax = 202 +/- 90.8 min
     AUC = 238 +/- 100 mcg x minute/mL                 AUC = 577 +/- 416 mcg x minute/mL
     Vd = 396 +/- 316 mL/kg                              Vd = 650 +/- 1842 mL/kg
     CL = 10 +/- 3.73 mL/minute/kg                         CL = 7.08 +/- 13 mL/minute/kg
     t1/2 = 7.52 +/- 5.48 min                              t1/2 = 35.9 +/- 21.5 min
 
Mean AUC and Cmax increased to 2.8- and 2.9-fold, respectively, at Week 22 compared to Week 0. Mean T1/2 increased from 7.5 min at Week 0 to 35.9 min at Week 22. These changes are likely related to the development of neutralizing antibodies in all patients receiving elosulfase alfa. Neutralizing antibody titers were not determined so the possibility of an association between neutralizing antibody titer and treatment efficacy is not known.

There are no adequate prospective studies of elosulfase alfa in pregnant women. Data from postmarketing reports and published case reports are insufficient to evaluate for elosulfase alfa-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies in rats and rabbits found no effects on embryo-fetal development when elosulfase alfa was given during the period of organogenesis; however, a dose-dependent increase in stillbirths was observed in rats and pups when the drug was given during organogenesis through lactation. Pregnancy can adversely affect the health of females affected with Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) and lead to adverse pregnancy outcomes for both mother and fetus. To monitor fetal outcomes of pregnant women exposed to elosulfase alfa, a Morquio A Registry is available that collects data on pregnant women treated with elosulfase alfa. Healthcare professionals are encouraged to register patients by contacting MARS@bmrn.com or calling 1-800-983-4587.[56716]

Use elosulfase alfa with caution in breast-feeding mothers. Elosulfase alfa is present in milk from treated rats so the drug is also likely present in human milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. To monitor data related to lactation and the outcomes of the breastfed child, the manufacturer maintains a Morquio A Registry that collects data on breast-feeding women with Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) who are receiving treatment with elosulfase alfa. Healthcare providers are encouraged to register patients by contacting MARS@bmrn.com or calling 1-800-983-4587.[56716]